Expression and Function of a Disintegrin and Metalloproteinases in Cancer-Associated Fibroblasts of Colorectal Cancer.
ADAM Proteins
/ biosynthesis
Animals
Biomarkers, Tumor
/ metabolism
Cancer-Associated Fibroblasts
/ metabolism
Cell Proliferation
Colorectal Neoplasms
/ metabolism
Disease Models, Animal
Disease Progression
Extracellular Matrix
/ metabolism
Fibroblasts
/ metabolism
Fibrosis
/ metabolism
Humans
Mice
Neoplasm Metastasis
Prognosis
Stromal Cells
/ metabolism
Tumor Cells, Cultured
Tumor Microenvironment
A disintegrin and metalloproteinase
Cancer-associated fibroblast
Colorectal cancer
Desmoplastic reaction
Journal
Digestion
ISSN: 1421-9867
Titre abrégé: Digestion
Pays: Switzerland
ID NLM: 0150472
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
10
2019
accepted:
11
10
2019
pubmed:
14
11
2019
medline:
7
8
2020
entrez:
14
11
2019
Statut:
ppublish
Résumé
Cancer tissues consist of cancer cells and stroma, the latter of which dictates cancer tissue microenvironment. We recently reported that the desmoplastic reaction (DR) pattern at the invasive front in colorectal cancer (CRC) is a promising prognostic indicator. However, the molecular mechanisms of DR formation and contribution to patients' prognosis remain unclear. The tumor tissue microenvironment composed of extracellular matrix (ECM), soluble factors (growth factors/cytokine/cytokine), and stromal cells controls tumor growth and spread. Among stromal cells, cancer-associated fibroblasts (CAFs) play a key role in development of the cancer tissue microenvironment, and they are responsible for DR formation. CAFs express a disintegrin and metalloproteinases (ADAMs), which modulate cancer tissue microenvironmental factors. We isolated CAFs and normal fibroblasts from colon tissues of patients with CRC and characterized them. CAFs showed the increased expression of several ADAM species including ADAM9, ADAM10, ADAM12, and ADAM17, and the expression was further increased on the ECM-coated plates. Our in vitro and in vivo studies using CAFs and CRC cells suggest that ADAM expression is associated with the morphological DR category, and ADAMs may affect cancer malignancy through tumor proliferation in CRC. Key Message: This review summarizes the present knowledge on ADAMs in cancer and describes our recent findings regarding the molecular biological background of DR mainly by focusing on ADAMs.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer tissues consist of cancer cells and stroma, the latter of which dictates cancer tissue microenvironment. We recently reported that the desmoplastic reaction (DR) pattern at the invasive front in colorectal cancer (CRC) is a promising prognostic indicator. However, the molecular mechanisms of DR formation and contribution to patients' prognosis remain unclear.
SUMMARY
CONCLUSIONS
The tumor tissue microenvironment composed of extracellular matrix (ECM), soluble factors (growth factors/cytokine/cytokine), and stromal cells controls tumor growth and spread. Among stromal cells, cancer-associated fibroblasts (CAFs) play a key role in development of the cancer tissue microenvironment, and they are responsible for DR formation. CAFs express a disintegrin and metalloproteinases (ADAMs), which modulate cancer tissue microenvironmental factors. We isolated CAFs and normal fibroblasts from colon tissues of patients with CRC and characterized them. CAFs showed the increased expression of several ADAM species including ADAM9, ADAM10, ADAM12, and ADAM17, and the expression was further increased on the ECM-coated plates. Our in vitro and in vivo studies using CAFs and CRC cells suggest that ADAM expression is associated with the morphological DR category, and ADAMs may affect cancer malignancy through tumor proliferation in CRC. Key Message: This review summarizes the present knowledge on ADAMs in cancer and describes our recent findings regarding the molecular biological background of DR mainly by focusing on ADAMs.
Identifiants
pubmed: 31722362
pii: 000504087
doi: 10.1159/000504087
doi:
Substances chimiques
Biomarkers, Tumor
0
ADAM Proteins
EC 3.4.24.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
18-24Informations de copyright
© 2019 S. Karger AG, Basel.